Background. During cold storage, some red blood cell (RBC) units age more rapidly than others. Yet, the Food and Drug Administration has set a uniform storage limit of 42 days. Objectives of this review are to present evidence for an RBC storage lesion and suggest that functional measures of stored RBC quality-which we call real age-may be more appropriate than calendar age. Methods. During RBC storage, biochemical substances and byproducts accumulate and RBC shape alters. Factors that influence the rate of degradation include donor characteristics, bio-preservation conditions, and vesiculation. Better understanding of markers of RBC quality may lead to standardized, quantifiable, and operationally practical measures to improve donor selection, assess quality of an RBC unit, improve storage conditions, and test efficacy of the transfused product. Results. The conundrum is that clinical trials of younger versus older RBC units have not aligned with in vitro aging data; that is, the units transfused were not old enough. In vitro changes are considerable beyond 28 to 35 days, and average storage age for older transfused units was 14 to 21 days. Conclusions. RBC product real age varies by donor characteristics, storage conditions, and biological changes during storage. Metrics to measure temporal changes in quality of the stored RBC product may be more appropriate than the 42-day expiration date. Randomized trials and observational studies are focused on average effect, but, in the evolving age of precision medicine, we must acknowledge that vulnerable populations and individuals may be harmed by aging blood.

Inhibition of ␤-site APP cleaving enzyme 1 (BACE1) is being pursued as a therapeutic target for treating patients with Alzheimer's disease because BACE1 is the sole ␤-secretase for generating ␤-amyloid peptide. Knowledge regarding the other cellular functions of BACE1 is therefore critical for the safe use of BACE1 inhibitors in human patients. BACE1 deficiency in mice causes hypomyelination during development and impairs remyelination in injured sciatic nerves. Since BACE1 is expected to be ubiquitously expressed, we asked whether axonal or Schwann cell BACE1 is required for optimal remyelination. By swapping sciatic nerve segments from BACE1-null mice with the corresponding wild-type nerve segments or vice versa, we tested how a deficiency of BACE1 in Schwann cells or axons affects remyelination. Our results show that BACE1 in axons and Schwann cells is similarly important for remyelination of regenerated axons. Nerve injury induces BACE1 transcription and protein levels are elevated in Schwann cells. Expression of type I neuregulin 1 (Nrg1), rather than type III Nrg1, was induced by Schwann cells, and the abolished Nrg1 cleavage in BACE1-null Schwann cells contributed to decreased remyelination of regenerated axons. Hence, this study is the first to demonstrate the equal importance of axonal and Schwann cell BACE1 for remyelination of injured nerves.

In this retrospective study, the authors found that ITB therapy is effective in reducing spasticity and related symptoms in ambulatory patients with MS. Because the use of ITB therapy is increasing in ambulatory patients with MS, randomized, prospective studies are important to help provide a more useful characterization of the effects of ITB therapy on ambulation.